Previous investigators, using 99mTc-DTPA aerosol as a marker to assess epithelial permeability in asthma, did not find an increased permeability in this group. However, they either failed to deliver the aerosol to the optimal site (bronchial mucosa, not alveoli) or failed to account for mucociliary clearance in analyzing their results. We studied 10 asthmatics and eight age-matched control subjects using a dosimeter (Spira-Elektra 2) and a carefully controlled breathing pattern to deliver aerosol to the subjects' airways. Two aerosols were delivered on separate days in each patient; 99mTc-DTPA aerosol, and 99mTc-HSA (human serum albumin), using similar breathing patterns to ensure reproducibility of the deposition pattern with the two aerosols. From measurements of retention versus time over a 1-h period, rate constants Ktot and Km were determined for the clearance of 99mTc-DTPA and 99mTc-HSA, respectively. By modelling the airways as a single compartment with two possible routes of clearance, we determined the permeability rate constant, Kp, as Ktot minus Km. There was no significant difference between Ktot in normal subjects and asthmatics; however, because of the slower mucociliary clearance in the asthmatic group, and the relative importance of mucociliary clearance in determining the washout of 99mTc-DTPA aerosol, there was a significant difference in airway permeability between the normal subjects and the asthmatics (t1/2 = 296 min +/- 141 SD and 126 min +/- 58, p less than 0.01, in normal subjects and asthmatics, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

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The influence of aerosolized atropine sulfate on lung airway mucus clearance was investigated in healthy human subjects who were nonsmokers. Mucus transport was measured with radiolabeled insoluble particles inhaled by mouth and deposited onto mucosal surfaces; subsequent retention of radiolabel was quantitated over a 4- to 5-h period by a noninvasive, posteriorly aligned, gamma camera. Placebo and atropine clearance tests were matched in a given subject for initial and for final (24-h postinhalation) deposition pattern of labeled aerosol at the onset and conclusion, respectively, of tracheobronchial particle clearance. In seven subjects mucociliary function was delayed after inhalation of 0.025 mg/kg body weight atropine sulfate as compared with placebo (0.9% NaCl). On the basis of the area under the activity versus time curves, retention times during atropine exceeded placebo times by more than 30% (p less than 0.01). At 90 min postatropine inhalation, the Vmax50 exceeded baseline values by 21% (p less than 0.01). Urine retention was present in one subject and xerostomia was present in all subjects after atropine. These data suggest that a single dose of atropine sulfate delivered topically to the airway surfaces delays the continuous flow of airway mucus in healthy subjects and that basal autonomic tone is an inherent factor for optimal secretion and/or removal of tracheobronchial secretions.